January 20, 2012
VIA ELECTRONIC DELIVERY
Louis B. Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
Mail Stop S3-02-01
7500 Security Blvd
Baltimore, MD 21244
Re: Centers for Medicare & Medicaid Services’ (CMS) public solicitation for comments on Coverage with Evidence Development (CED)
Dear Dr. Jacques:
The following comments on the CED Public Solicitation1 are submitted on behalf of Eli Lilly and Company (“Lilly”). Lilly is one of the country’s leading innovation-driven, research-based pharmaceutical and biotechnology corporations. Our company is devoted to seeking answers for some of the world's most urgent medical needs through discovery and development of breakthrough medicines and technologies and through the health information we offer. Ultimately, our goal is to develop products that save and improve patients’ lives.
Lilly shares CMS’ desire to improve health outcomes and accelerate access to medical technology for Medicare beneficiaries.2
Lilly invests significant resources in research and development to build evidence to help target our medical technologies for those patients who will benefit most. Our investment in clinical research and development continues through a product’s life cycle, well beyond the initial studies required to meet a rigorous FDA approval process.
Lilly appreciates CMS’ attempt to improve the CED process, and build on the principles governing CED that were established in the 2006 guidance document. We believe that these principles are sound and should continue to be the foundation for any improved CED process. We urge the agency to include these core principles in any revised CED guidance that may be issued. The eight principles governing CED, as outlined in the 2006 guidance, are as follows:
- National Coverage Determinations (NCDs) requiring CED will occur within the NCD processes, which is transparent and open to public comment.
- CED will not be used when other forms of coverage are justified by the available evidence.
- CED will in general expand access to technologies and treatments for Medicare beneficiaries.
- CMS expects to use CED infrequently.
- CED will lead to the production of evidence complementary to existing medical evidence.
- CED will not duplicate or replace the FDA’s authority in assuring the safety, efficacy, and security of drugs, biological products, and devices.
- CED will not assume the NIH’s role in fostering, managing, or prioritizing clinical trials.
- Any application of CED will be consistent with federal laws, regulations, and patient protections.3
Lilly supports these principles as they protect and improve beneficiary access to important technologies and focus on the development of useful clinical evidence that is complimentary to existing evidence.
Lilly is concerned with CMS’ broad statement that “many new technologies are developed with insufficient attention to addressing the needs of the Medicare beneficiary population.”4 Although this may be true for some medical technologies, it is rarely true for drugs and biologics used by the Medicare population. These therapies are subject to a rigorous FDA approval process, and their approved prescribing information clearly indicates the population for which each therapy is approved based on data supporting that approval. Consistent with CMS’ 2006 CED principles, CMS should not duplicate or replace the FDA’s authority by requiring additional evidence of a drug or biological for its approved indications. CED is rarely, if ever, appropriate for the FDA-approved uses of drugs and biologics that are approved for use in the Medicare population based on FDA and often advisory panel review of data reflecting outcomes in the Medicare population.
Lilly believes CED is not necessary if an FDA Risk Evaluation and Mitigation Strategy (REMS) registry is in place. At most, when CMS believes CED is warranted, CED should simply integrate necessary data requirements into and extract relevant analyses from the REMS registry. This would allow requestors to implement CED efficiently in those situations where the FDA has required post-approval data collection. This process would provide coverage to beneficiaries while the evidence is being collected, thus avoiding duplicative and wasteful efforts for purpose of CED.
Additionally, CMS should proactively remove any pre-existing broad national non-coverage exclusionary policies, such as the current Positron Emission Tomography (PET) coverage policy (220.6), which explicitly non-covers new, innovative agents never reviewed by CMS from coverage. These exclusionary policies inappropriately render immediate non-coverage decisions on any new FDA-approved technology. In effect, such policies constitute an affirmative position that the imaging agent has failed to meet statutory criteria for medical necessity, even though the agent has undergone no review by Medicare. Exclusionary coverage policies create barriers to medical innovation that can discourage future investments in research and development.
New diagnostic radiopharmaceuticals will undergo the full rigors of the FDA-approval process. Furthermore, new proprietary agents are supported by manufacturers who invest in post-approval studies to broaden the evidence base and provide training and education on the appropriate use of the new technology. For these reasons, Lilly believes new diagnostic radiopharmaceuticals should be available to Medicare beneficiaries upon FDA approval and that the current exclusionary language is not appropriate. CED should be applied rarely to new radiopharmaceuticals. Lilly requests that CMS make these policy changes which will avoid denying important access to new innovations which will benefit the Medicare population.
We provide specific comments on each of the three areas specifically requested by CMS below.
1. Implementation of CED through the NCD or other avenues under Part A and Part B.
CMS has expressed interest in expanding application of CED beyond the NCD process. Lilly supports the first principle published in the 2006 guidance: “NCDs requiring CED will occur within the NCD processes, which is transparent and open to public comment.” Any application of CED must be developed in a clear and predictable manner, with opportunity for public comment, to ensure that CMS reaches an appropriate decision. The NCD process is designed to provide for this, whereas other processes might not.
In the rare situations when CMS chooses to apply CED, CMS can, however, substantially accelerate the launch of CED. When the manufacturer is in agreement, Lilly urges CMS to move directly to CED through a streamlined NCA/NCD process starting with a proposed coverage decision. This process, which would work under CMS’ existing framework, will eliminate inefficiency and waste and make new technologies with agreed upon evidence gaps available to beneficiaries within 90 days of FDA approval. CMS can propose an NCD in this manner, because § 1862(l)(3) of the Social Security Act requires only a single thirty-day comment period which occurs after posting a proposed decision memorandum. CMS has proposed NCDs in this way in cases where an initial six month analysis opened by public comment would serve no useful purpose (for example, in a reconsideration of the Clinical Trial Policy and in a requested NCD for home sleep testing for obstructive sleep apnea. 5) CMS would receive little difference in the way of public comment by announcing it intends to open CED on a specific therapy and indication, versus simply presenting the public the proposal for CED, in the form of an initial NCA.
When CED is warranted by CMS, we urge CMS to work with key stakeholders including the relevant clinical societies and the manufacturer prior to opening an NCD to design a CED process that will clearly define a pathway to begin and end CED on a technology after the appropriate amount of evidence has been collected. These parties should work together to develop, design and implement the study/registry protocols.
Lilly believes this approach is a much better mechanism to allow streamlined NCD than allowing CED through local Medicare contractors. Allowing CED to occur under a local coverage determination introduces additional complexity, duplication, and cost for all stakeholders involved. There are a number of substantial drawbacks to offering CED through local contractors, and they would be very difficult to remedy. Only by implementing CED at the national level can CMS bypass a number of drawbacks related to small study sample sizes, limited agency resources and duplicative clinical trials with incompatible endpoints. Furthermore, CED at the local level would be unreasonably burdensome for sponsors who may be required to work with as many as fifteen different Medicare Administrative Contractors (MACs), potentially leading to poor study enrollment and inconsistent access for Medicare beneficiaries. CMS has stated that CED should be used infrequently and not to duplicate or replace the FDA’s authority, but these principles will be difficult to enforce across a wide diversity of contractors and with local medical directors who have widely variable levels of topic-specific expertise. In general, as noted earlier, CED will not be necessary for FDA-approved drugs and biologicals, and should a potential exception arise, it should best be reviewed by experienced CMS staff and with the opportunity for national comment. Unlike surgical procedures or physical therapies, which require manual expertise, the efficacy of drugs does not vary locally.
2. Potential impact of CED on the Medicare program and its beneficiaries.
The principles established in the 2006 guidance document can help ensure that CED improves appropriate beneficiary access to innovation. As Lilly has requested, CMS should use the 2006 CED principles as the foundation for an improved CED policy that seeks to develop additional evidence to expand access to technologies in those rare instances where available evidence is insufficient.
Absent these principles, CED could create undue burden on beneficiaries, healthcare providers, and manufacturers. For Medicare beneficiaries, local CED likely would result in confusion and inefficiencies while generating a much smaller base of additional evidence. Patient access to life-saving technologies could be delayed with implementation of local CED which may result in lower health outcomes and additional cost to the healthcare system through potential use of less effective treatment. In addition, local CED could lead to regional access disparities resulting in discrimination against beneficiaries in certain region and/or rural geographies.
3. Suggested approaches to CED to maximize benefit to Medicare beneficiaries
We summarize our comments by stating four key principles. First, as stated above, we believe that maximizing CED benefit to Medicare beneficiaries will occur only if the principles established in the 2006 guidance document form the basis of any revision to the CED. CMS should apply CED rarely, especially in the case of drugs and biologics. In addition to the existing 2006 CED principles, Lilly urges CMS, when CMS believes CED is warranted and the manufacturer is in agreement, to move directly to CED through a streamlined NCA/NCD process starting with a proposed coverage decision. This process, which would work under CMS’ existing framework, will eliminate inefficiency and waste and make new technologies with agreed upon evidence gaps available to beneficiaries with 90 days of FDA approval. Local CED should not be pursued at this time.
Second, Lilly recommends that CED agreements should be in coordination with interested stakeholders, and expressly include the manufacturers and any involved professional/clinical societies. Manufacturers and/or key stakeholders should work directly with CMS to develop, design and implement the study. Agreements should allow for confidentiality provisions as agreed to by all parties, including appropriate distinctions for both financial and scientific information. CMS should allow industry sponsors (such as a device, diagnostic or pharmaceutical/biologic manufacturer) to conduct a CED study directly, in addition to funding the development and conduct of the study. Manufacturers and other stakeholders should be given blinded access to the final data set for their own analyses.
Third, CED should only be applied when the supposed data uncertainty is specific and feasible to define, and when the additional evidence required is obtainable in a reasonable and cost-effective manner, including the cost of time for program management by physicians, pharmacists, patients, and other stakeholders. The evidence gap as well as the design and methods of evaluation must be clearly stated in advance of the collection of new evidence. Sponsors and decision makers must be in agreement on the decision points and the quality of the evidence to be obtained before the program is implemented. Evidence must fit the purpose of CED, which means it should be relevant, narrowly defined, and timely. The timing for reporting results should be evaluated on a case-by-case basis and should include consideration of the impact of future treatments. CED should have a clearly defined beginning and end.
Fourth, and finally, Lilly feels strongly that CED should not delay access and at minimum, CMS coverage under the CED agreement should be consistent with product’s FDA label. While a technology is being evaluated under CED, we encourage CMS to make coverage available to all Medicare beneficiaries, not just those beneficiaries who are participating in the CED- sponsored registry or trial. Lilly believes that the important evidence being collected under CED should not have the negative consequence of denying beneficiaries who do not have access to the CED registry or trial the potential benefit of the innovative technology during the CED process. CMS should proactively remove existing non-coverage policies, such the current Positron Emission Tomography (PET) coverage policy, which explicitly excludes new agents from coverage. Forward-looking CED agreements can be in place prior to the date of FDA approval to facilitate access to beneficiaries upon FDA approval. Once a product's indication is determined by FDA approval, the product’s label should be taken as the definitive view of the product's characteristics for the purpose of CED design.
Lilly appreciates the opportunity to comment on the future of CED. We look forward to continuing to work with CMS to improve access to breakthrough medicines and technologies that improve Medicare beneficiaries’ lives. Please feel free to contact Derek Asay at 908-268-8720 if you have any questions or need any additional information. Thank you for your attention to this very important matter.
Derek L. Asay
Director, Government Strategy, Federal
Accounts and Quality
Sean P. Donohue
Senior Director, Federal Affairs
1 CED Public Solicitation, Nov. 7, 2011, http://www.cms.gov/medicare-coverage-database/details/medicare-coverage-document-details.aspx?MCDId=8&McdName=CED+Public+Solicitation&mcdtypename=Guidance+Documents&MCDIndexType=1&bc=AgAEAAAAAAAA&.
3 Guidance for the Public, Industry, and CMS Staff, National Coverage Determinations with Data Collection as a Condition of Coverage: Coverage with Evidence Development, July 12, 2006.
4 CED Public Solicitation.
5 See, e.g., NCA Tracking Sheet for Clinical Trial Policy (CAG-00071R2), in which the formal request was accepted and the review initiated on July 19, 2007, and the proposed decision memorandum was also released on July 19, 2007. At the beginning of this tracking sheet CMS explains its rationale for releasing the proposed decision memorandum on the same date that it opened the NCD. See also NCA Tracking Sheet for Sleep Testing for Obstructive Sleep Apnea (CAG-00405N).